Talazoparib (BMN-673) is a poly (ADP-ribose) polymerase (PARP) inhibitor which blocks PARP by selective binding and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. BMN673 is indicated for the treatment of hematological malignancies, genetically defined solid tumors and metastatic breast cancer. After trials for advanced hematological malignancies and for advanced or recurrent solid tumors. It is now in phase 3 for metastatic germline BRCA mutated breast cancer. Trial estimated to complete in June 2016.
Talazoparib is described chemically as (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one, and has the structural formula shown as Formula 1:

International patent application publication No. WO 2010/017055 discloses dihydropyridophthalazinone inhibitors of poly (ADP-ribose) polymerase (PARP). 4-amino-6-fluoroisobenzofuran-1(3H)-one and 4-fluorobenzaldehyde are used as starting materials for preparation of talazoparib; and the reaction of the chiral separation is arranged in the final step, and the chiral separation is performed using super-fluid chromatography (SFC) with chiral column and methanol and CO2 as the eluents, which seriously reduces the yield of the final product.

International patent application publication No. WO 2015/069851 discloses triazole intermediates useful in the synthesis of protected N-alkyltriazolecarbaldehydes. 1-methyl-1H-1,2,4-triazole and 6-fluoro-4-nitroisobenzofuran-1(3H)-one are used as starting materials for preparation of talazoparib; and the reaction condition need to be cooled to about −30° C., and increases the difficulty of industrial production.

Therefore, the current synthesis method of talazoparib is still to be improved.